The activities of biotin-dependent carboxylases fall in deficiency, resulting in impaired gluconeogenesis, with accumulation of lactate, pyruvate, and alanine, and impaired lipogenesis, with accumulation of acetyl CoA, resulting in ketosis. There are also changes in the fatty acid composition of membrane lipids. A variety of abnormal organic acids are excreted by both biotin-deficient patients and experimental animals (as shown in Table 11.1).
There is accumulation of the apoenzymes of biotin-dependent carboxylases in deficiency. Response to repletion is rapid, as a result of activation of the apoenzymes; activation of biotin-dependent apoenzymes in vitro may provide an index of status (Section 11.4).
22.214.171.124 Glucose Homeostasis in Biotin Deficiency The impairment of pyruvate carboxylase in biotin deficiency results in impaired gluconeogenesis. Additionally, biotin deficiency results in a lowering of the NADH:NAD ratio and further reduction of gluconeogenesis by impairment of glyceraldehyde- 3-phosphate dehydrogenase activity. This impairment of gluconeogenesis may result in fatal hypoglycemia in marginally biotin-deficient chicks subjected to a relatively minor metabolic stress (Section 11.3.2).
Rather than the expected hypoglycemia, biotin deficiency may sometimes be associated with hyperglycemia, because of reduced activity of glucokinase. As discussed in Section 11.2.4, this results in both decreased clearance of glucose by the liver and also decreased secretion of insulin in response to hy-perglycemia. In streptozotocin diabetic animals, the administration of biotin improves glucose tolerance as a result of the induction of glucokinase (Zhang etal., 1997).
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